We have begun this project by targeting 40 candidate genes identified by the Undiagnosed Diseases Program. Initially we used TALEN technology to target alleles. In collaboration with Dr. Raman Sood and the NHGRI zebrafish core we have shifted the entire program to CRISPR/Cas9 mutagenesis and have shown this approach is more than 6 times more efficient in generating mutants. We have identified germline transmitted mutations in all 40 genes. We will raise these fish and inbreed carrier siblings. Each gene will be phenotyped and any observable phenotypes will be compared to the human pathology. Of the first 23 tested, we have seen phenotypes in 2 lines. We are working to complete the initial screening for all 40 genes as well as begin to characterize the lines that display a pathological phenotype.